This Research Career Award application describes a career development plan for Dr. Paul R. Bohjanen to further develop his research program directed toward understanding the role of mRNA degradation in regulating T lymphocyte gene expression. Dr. Bohjanen recently completed clinical training in infectious diseases and started his first faculty position as an Assistant Professor in July of 2000. His proposed research is based on the hypothesis that mRNA degradation plays an important role in regulating T lymphocyte gene expression. The first specific aim is to identify T lymphocyte genes that are regulated at the level of mRNA degradation. Microarray technology will be used to profile mRNA transcripts expressed in T lymphocytes based on their rates of mRNA decay and to identify transcripts whose rate of mRNA decay changes upon cellular activation. Specific mRNA transcripts whose rate of decay is regulated will be characterized further to identify novel sequence elements and trans-acting factors that regulate mRNA decay. A subset of T lymphocyte transcripts, including cytokine transcripts and certain proto-oncogene transcripts, contain sequences known as AU-rich elements (AREs) that are important regulators of mRNA degradation. The proteins HuA and TTP bind specifically to AREs and thereby regulate mRNA degradation. The second specific aim is to characterize the expression and function of these proteins in T lymphocytes. The University of Minnesota provides a strong and interactive intellectual environment for Dr. Bohjanen to develop his research program. He has numerous interactions with colleagues who have expertise in related research areas including T lymphocyte immunology, virus infection of T lymphocytes, and the biochemistry of RNA-protein interactions. His participation in research conferences within the Center for Immunology, Department of Microbiology, and the RNA biology community at the university will provide an ongoing critical evaluation of work performed in his laboratory. Dr. Bohjanen has adequate space and resources for carrying out the proposed experiments, and facilities are available through the Biomedical Genomics Center to perform the proposed microarray experiments. The Independent Scientist Award would provide Dr. Bohjanen with additional support and protected time for research to enable him to establish a productive research career.